Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis

Abstract

Objectives To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman’s rank or Pearson’s) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.

Neuropsychiatric Systemic Lupus Erythematosus: Molecules Involved in Its Imunopathogenesis, Clinical Features, and Treatment

“…ECs are important for regulating blood pressure and play important roles in coagulation, fibrinolysis, angiogenesis, and immune cell activation via both physiological and pathological processes [ 99 ]. The modulation of endothelial cells via the adaptive and innate immune systems plays an integral role in autoimmune diseases, as endothelial cells promote chronic inflammation via angiogenesis, attracting immune cells, and antigen presentation [ 100 ]. Anti-endothelial cell antibodies (AECA) are a heterogeneous group of autoantibodies directed against structural endothelial proteins, along with antigens on endothelial cells [ 101 ].…”

Neuropsychiatric Systemic Lupus Erythematosus: Antibodies Involved, Clinical Characteristics and Treatment

“…ECs are important for regulating blood pressure and play important roles in coagulation, fibrinolysis, angiogenesis, and immune cell activation via both physiological and pathological processes [80]. Modulation of endothelial cells via the adaptive and innate immune systems plays an integral role in autoimmune diseases, as endothelial cells promote chronic inflammation via angiogenesis, attracting immune cells, and antigen presentation [81]. Antiendothelial cell antibodies (AECA) are a heterogeneous group of autoantibodies directed against structural endothelial proteins, along with antigens on endothelial cells [82].…”

The Relationship between TNF-a, IL-35, VEGF and Cutaneous Microvascular Dysfunction in Young Patients with Uncomplicated Type 1 Diabetes

“…This means that small changes in its concentration influence physiological effects [4,15]. Some research has shown that the serum concentration of VEGF corresponds with the clinical activity of various diseases, including tumor growth, atherosclerosis of the coronary arteries, Kawasaki disease, neovascularization of synovial tissue in rheumatoid arthritis and diabetic microangiopathy [16][17][18][19]. In patients with DM1, hyperglycemia stimulates VEGF upregulation.…”